rs464058

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001098511.3(KIF2A):c.2013+81A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 775,798 control chromosomes in the GnomAD database, including 24,889 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 4884 hom., cov: 33)

Exomes 𝑓: 0.25 ( 20005 hom. )

Consequence

KIF2A
NM_001098511.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0120

Publications

4 publications found

Variant links:

Genes affected

KIF2A (HGNC:6318): (kinesin family member 2A) The protein encoded by this gene is a plus end-directed motor required for normal mitotic progression. The encoded protein is required for normal spindle activity during mitosis and is necessary for normal brain development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

KIF2A links:

ENSG00000288643 (HGNC:):

ENSG00000288643 links:

DIMT1 (HGNC:30217): (DIM1 rRNA methyltransferase and ribosome maturation factor) The protein encoded by this gene is a methyltransferase that is responsible for dimethylation of adjacent adenosines near the 18S rRNA decoding site. The encoded protein is essential for ribosome biogenesis, although its catalytic activity is not involved in the process. The yeast ortholog of this protein functions in the cytoplasm while this protein functions in the nucleus. [provided by RefSeq, Jan 2017]

DIMT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 5-62377843-A-G is Benign according to our data. Variant chr5-62377843-A-G is described in ClinVar as Benign. ClinVar VariationId is 682886.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
KIF2A	NM_001098511.3 link	c.2013+81A>G	intron_variant	Intron 19 of 20	ENST00000407818.8	NP_001091981.1
KIF2A	NM_004520.5 link	c.1899+81A>G	intron_variant	Intron 18 of 19		NP_004511.2
KIF2A	NM_001243953.2 link	c.1842+81A>G	intron_variant	Intron 18 of 19		NP_001230882.1
KIF2A	NM_001243952.2 link	c.1818+81A>G	intron_variant	Intron 19 of 20		NP_001230881.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIF2A	ENST00000407818.8 link	c.2013+81A>G		intron_variant	Intron 19 of 20	1	NM_001098511.3	ENSP00000385000.3
ENSG00000288643	ENST00000509663.2 link	n.64+71307A>G		intron_variant	Intron 1 of 5	3		ENSP00000502199.1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38122

AN:

152038

Hom.:

4884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.265

Gnomad AMI

AF:

0.425

Gnomad AMR

AF:

0.204

Gnomad ASJ

AF:

0.285

Gnomad EAS

AF:

0.231

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.256

Gnomad OTH

AF:

0.222

GnomAD4 exome

AF:

0.249

AC:

155587

AN:

623642

Hom.:

20005

AF XY:

0.249

AC XY:

80709

AN XY:

324594

show subpopulations

African (AFR)

AF:

0.264

AC:

4088

AN:

15480

American (AMR)

AF:

0.198

AC:

4150

AN:

20950

Ashkenazi Jewish (ASJ)

AF:

0.283

AC:

4640

AN:

16388

East Asian (EAS)

AF:

0.280

AC:

8595

AN:

30740

South Asian (SAS)

AF:

0.191

AC:

8257

AN:

43144

European-Finnish (FIN)

AF:

0.258

AC:

11485

AN:

44476

Middle Eastern (MID)

AF:

0.278

AC:

944

AN:

3396

European-Non Finnish (NFE)

AF:

0.253

AC:

105885

AN:

418002

Other (OTH)

AF:

0.243

AC:

7543

AN:

31066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5659

11318

16976

22635

28294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2144

4288

6432

8576

10720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.251

AC:

38139

AN:

152156

Hom.:

4884

Cov.:

AF XY:

0.250

AC XY:

18630

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.265

AC:

10987

AN:

41518

American (AMR)

AF:

0.204

AC:

3122

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.285

AC:

989

AN:

3468

East Asian (EAS)

AF:

0.231

AC:

1198

AN:

5190

South Asian (SAS)

AF:

0.183

AC:

883

AN:

4820

European-Finnish (FIN)

AF:

0.249

AC:

2626

AN:

10562

Middle Eastern (MID)

AF:

0.303

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.256

AC:

17390

AN:

67984

Other (OTH)

AF:

0.221

AC:

467

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1487

2975

4462

5950

7437

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.252

Hom.:

788

Bravo

AF:

0.250

Asia WGS

AF:

0.198

AC:

691

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.75

(source)

DANN

Benign

0.62

PhyloP100

0.012

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over